Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone

Abstract

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-in ammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ coadministration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a signi cant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs intoxicated rats. Furthermore, TQ coadministration decreased the hepatic and renal pro-in ammatory mediators represented by, IL-1β, TNF-α, TGF-β, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These ndings were con rmed by the histopathological examination of hepatic and renal tissues. Our data a rmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-in ammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…Their work verified the excellent anticancer properties of TQs [ 57 ]. Murphy et al has also proposed a targeted delivery method using phospholipid shells to deliver TQ to breast tumor lesion sites based on its natural hydrophobicity [ 56 ].…”

Thymoquinone alleviates cisplatin-induced kidney damage by reducing apoptosis in a rat model

“…Kaymak et al [ 9 ] examined the effects of doxorubicin on kidney cell apoptosis and caspase-3, IL-17, GRP78, and TNF-α expression: in a doxorubicin-induced renal injury model, thymoquinone reduced the expression of these proteins, thus ameliorating renal damage by inhibiting apoptosis. Thymoquinone protects against silver nanoparticle-induced cytotoxicity via an anti-apoptotic effect: when administered along with silver nanoparticles, thymoquinone reduced Bax and increased Bcl-2 levels [ 20 ]. These studies suggest that thymoquinone has renoprotective effects, inhibiting apoptosis, when administered with nephrotoxic drugs.…”

“…Only one study has included Bcl-2 and Bax expression as outcomes [ 20 ]. Bcl-2 and Bax, which have opposing effects, form an important regulatory protein pair in the mitochondria-mediated endogenous apoptosis pathway [ 23 ].…”

“…Cisplatin-induced kidney damage is closely associated with apoptosis. Nonetheless, few studies about thymoquinone have addressed the mechanisms of anti-apoptotic action, based on a PUBMED search [ 7 , 9 , 10 , 13 , 20 ]. Many preclinical studies have confirmed that it can ameliorate drug-induced kidney injury, with such research focusing on its antioxidant and anti-inflammatory mechanisms [ 21 ].…”

Effect of Edge Activator Combinations in Transethosomal Formulations for Skin Delivery of Thymoquinone via Langmuir Technique

“…Thymoquinone (TQ), 2-Methyl-5-(propan-2-yl) cyclohexa-2,5-diene-1,4-dione, is the main bioactive component of the volatile oil of Nigella sativa seeds [1]. It has been used in conventional medicine as an antioxidant, antimicrobial, anti-inflammatory, and anticancer agent [2][3][4][5][6]. For example, TQ has shown potential for treating acne vulgaris, pigmentation, vitiligo, hypersensitivity reactions, psoriasis, and even the early stages of skin tumorigenesis [7][8][9].…”